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WO2007018278A1 - Inhibiteur de l’apparition et de la progression du cancer hépatique - Google Patents

Inhibiteur de l’apparition et de la progression du cancer hépatique Download PDF

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Publication number
WO2007018278A1
WO2007018278A1 PCT/JP2006/315893 JP2006315893W WO2007018278A1 WO 2007018278 A1 WO2007018278 A1 WO 2007018278A1 JP 2006315893 W JP2006315893 W JP 2006315893W WO 2007018278 A1 WO2007018278 A1 WO 2007018278A1
Authority
WO
WIPO (PCT)
Prior art keywords
cirrhosis
isoleucine
leucine
patients
valine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2006/315893
Other languages
English (en)
Japanese (ja)
Inventor
Yukio Nihei
Sonoko Ishizaki
Akiko Okajima
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ajinomoto Co Inc
Original Assignee
Ajinomoto Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ajinomoto Co Inc filed Critical Ajinomoto Co Inc
Priority to JP2007529631A priority Critical patent/JP5067160B2/ja
Publication of WO2007018278A1 publication Critical patent/WO2007018278A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a drug for suppressing the occurrence and progression of liver cancer in cirrhosis patients with diabetes and in patients with cirrhosis having a high Z or BM I value.
  • Cirrhosis is caused by hepatitis C virus (HCV) -related monthly cirrhosis (C-type cirrhosis), hepatitis B virus (HBV) -related cirrhosis (type B cirrhosis), alcoholic cirrhosis, and others (non) B non-C type, special type, etc.).
  • HCV hepatitis C virus
  • HBV hepatitis B virus
  • alcoholic cirrhosis alcoholic cirrhosis
  • others non-C type, special type, etc.
  • HCV and HBV may be infected simultaneously (HBV 'HCV mixed type).
  • HCV and HBV may be infected simultaneously (HBV 'HCV mixed type).
  • cirrhosis patients with hepatitis C virus (hereinafter also referred to as hepatitis C virus-positive cirrhosis patients) are the most common.
  • K. I kedaeta 1, “Hepatology” (1 99 3) 1 8: 47— 5 3) the incidence of liver cancer in patients with type C cirrhosis Unlike patients with cirrhosis, they reported a steady increase over time. In addition, it is said that about 70-80% of liver cancer is caused by hepatitis C virus infection.
  • liver function decline due to cirrhosis may lead to impaired glucose processing and abnormal glucose metabolism, so there are many patients with cirrhosis who also have diabetes.
  • liver cancer occurs with a high probability.
  • BCAA branched-chain amino acids
  • Ribatato (registered trademark) is a preparation consisting of three branched chain amino acids of isoleucine, leucine and valine. By supplementing the branched chain amino acids in an appropriate ratio, the Fischer ratio is corrected and serum Power, a drug developed with the aim of increasing albumin concentration and improving the pathophysiology, and knowing its effects on inhibiting the development and progression of liver cancer in patients with cirrhosis and diabetes ,.
  • the problem to be solved by the present invention is to provide a drug or the like having an effect of inhibiting the development and progression of liver cancer in patients with cirrhosis complicated with diabetes.
  • Another object of the present invention is to provide a drug or the like having an effect of suppressing the development and progression of liver cancer in patients with cirrhosis having a high BMI value.
  • the present inventors have found that cirrhosis associated with diabetes has occurred in a composition comprising three branched chain amino acids of isoleucine, leucine and valine or their salts as active ingredients.
  • the present inventors have found that there is an effect of suppressing the occurrence / progress of liver cancer in patients and the effect of suppressing the occurrence / progression of liver cancer in patients with cirrhosis having a high BMI value, thereby completing the present invention.
  • the present invention includes the following items.
  • An inhibitor of hepatocarcinogenesis / progress for cirrhosis patients with diabetes comprising three branched-chain amino acids of isoleucine, leucine, and valine, or their salts as active ingredients.
  • a hepatocarcinogenesis / progression inhibitor for liver cirrhosis patients having a BMI value of 25 or more, comprising three branched chain amino acids of isoleucine, leucine, and valine or salts thereof as active ingredients.
  • liver cancer occurrence / progress inhibitor according to any one of [1] to [3], wherein the cirrhosis is decompensated cirrhosis.
  • the weight ratio of isoleucine, leucine, and parin or a salt thereof is 1: 1.5 to 2.5: 0.8 to 1.7, according to [1] to [4]
  • [6] The hepatocarcinogenesis ⁇ progression inhibitor according to any one of [1] to [5], wherein the daily dose is 2 g to 50 g.
  • [7] Use of three branched-chain amino acids or their salts, isoleucine, leucine, and parin, for the manufacture of a liver cancer development / progress inhibitor for cirrhosis patients with diabetes mellitus.
  • the cirrhosis patient is a patient positive for hepatitis C virus
  • liver cirrhosis associated with diabetes comprising an effective amount of three branched-chain amino acids or salts thereof, isoleucine, leucine, and valine, and a pharmaceutically acceptable carrier.
  • a cirrhotic patient having a BMI value of 25 or more, comprising an effective amount of three branched-chain amino acids or salts thereof, isoleucine, leucine, and valine, and a pharmaceutically acceptable carrier A pharmaceutical composition for inhibiting the development of liver cancer.
  • Figure 1 shows the cumulative non-incidence of liver cancer in diabetic patients with HCV-positive cirrhosis who were treated with diet and rebact.
  • Figure 2 shows the cumulative non-incidence of liver cancer in patients with BM I ⁇ 25 cirrhosis treated with dietary treatment and leapact.
  • the present invention relates to a liver cancer development-proliferation inhibitor and a Z or BM I value for patients with cirrhosis complicated with diabetes, comprising three branched chain amino acids of isoleucine, leucine, and valine or salts thereof as active ingredients.
  • the present invention provides an agent for suppressing the development of liver cancer for patients with high cirrhosis (hereinafter, these preparations are also referred to as agents of the present invention).
  • the present invention also provides an effective amount of the above-mentioned branched chain amino acid or a salt thereof, and a pharmaceutically acceptable carrier, and a pharmaceutical composition for inhibiting the development of liver cancer for patients with cirrhosis complicated with diabetes. And a pharmaceutical composition for inhibiting the development and progression of liver cancer for patients with cirrhosis having a high Z or BM I value (hereinafter, these preparations are also referred to as the composition of the present invention).
  • the present invention provides the above-mentioned agent of the present invention, and a description that describes the agent that states that the agent can be used or should be used to suppress the occurrence and progression of liver cancer.
  • compositions containing three amino acids, isoleucine, leucine, and valine, as an active ingredient improves hypoalbuminemia in cirrhosis patients.
  • a decrease in serum albumin is not an application condition.
  • the liver is known to have a large functional reserve, but among patients with cirrhosis, this functional reserve is significantly reduced, and gastrointestinal bleeding, ascites, encephalopathy, infections, etc. appear
  • the disease name decompensated cirrhosis is used.
  • the disease name of compensatory cirrhosis is used for the stage in which the functional reserve has not decreased so much.
  • the medicament and composition of the present invention are effective in suppressing or curing the development of liver cancer in patients with cirrhosis complicated with diabetes.
  • the cause of cirrhosis is not particularly limited, but may be caused by virus-related hepatitis.
  • the drug and composition are used for hepatitis C complicated with diabetes. It is effective in suppressing or curing the development / progression of liver cancer in patients with IL-positive cirrhosis, and more effective in cases where such cirrhosis is decompensated cirrhosis.
  • HCV and HBV infection can be determined by measuring HCV antibodies (commercially available HCV antibody measurement kit) and HBs antigens (RIA method, EIA method, etc.). Since some patients with cirrhosis are positive for HCV antibody negative 14 and HCV-RNA by the PCR method, HCV-RNA measurement by the PCR method is more useful for HCV antibody-negative patients. Patients with cirrhosis who are confirmed to be positive by the above methods or other methods that can confirm HCV or HBV infection must be HCV type / HBV type mixed liver cirrhosis patients. Is identified.
  • a C-type hepatitis virus-positive cirrhosis patient is a cirrhosis patient confirmed to be infected with HCV, and a cirrhosis patient derived from (related to) hepatitis C.
  • “concurrent with diabetes” refers to a state in which glucose tolerance is abnormal due to cirrhosis. More specifically, fasting blood glucose is 140 mgZd 1 or more, as needed Blood glucose level is 2 or more 20 Omg / d 1 or more, or OGTT (transglucose tolerance test), venous plasma glucose concentration is 11 Omg / fasting d 1 or more, 1 hour straight 16 Omg d 1 or more and 2 hour value 12 OmgZd 1 or more.
  • the agents and compositions of the present invention are effective in suppressing the development and progression of liver cancer in patients with cirrhosis having a high BM I value.
  • the cause of cirrhosis is not particularly limited, and hepatic cirrhosis derived from viral hepatitis, alcoholic cirrhosis, etc.
  • the BM I (Body ma ssindex) value is one of the methods for determining the degree of obesity, and is obtained by weight (kg) / ⁇ height (m) ⁇ 2 .
  • the standard value of BMI value is 22.0, and it is generally considered that obesity occurs when BMI value exceeds 25.
  • the medicament and composition of the present invention are particularly effective in patients with cirrhosis whose BMI value is 25 or more. Furthermore, it is more effective when the cirrhosis is decompensated cirrhosis.
  • Isoleucine, leucine, and valine which are the active ingredients (branched chain amino acids) of the drug and composition of the present invention, can use any of L-integral, D-isomer, and DL-isomer, preferably L-isomer, DL-isomer And more preferably L-form.
  • Isoleucine, leucine and valine can be used not only in free form but also in salt form. Examples of the salt form include acid addition salts and salts with bases, and it is preferable to select a pharmaceutically acceptable salt of isoleucine or leucine opium valine.
  • acids that are added to isoleucine, leucine, and parin to form pharmaceutically acceptable salts include inorganic salts such as hydrogen chloride, hydrogen bromide, sulfuric acid, and phosphate, acetic acid, lactic acid, kenic acid, Organic salts such as tartaric acid, maleic acid, fumaric acid or monomethyl sulfuric acid can be mentioned.
  • pharmaceutically acceptable bases for isoleucine, oral isine and parin include, for example, metal hydroxides or carbonates such as sodium, potassium and calcium, and inorganic bases such as ammonia.
  • salts with organic bases such as salts, ethylenediamine, propylenediamine, ethanolamine, monoalkylethanolamine, dialkylethanolamine, diethanolamine, and triethanolamine.
  • the drug and composition according to the present invention contain three kinds of branched-chain amino acids of isoleucine, leucine, and valine or salts thereof as active ingredients.
  • the mixing ratio of these three kinds of amino acids depends on the ratio of each amino acid.
  • the weight ratio is usually in the range of 1: 1.5 to 2.5: 0.8 to 1.7, particularly preferably 1: 1.9 to 2.2: 1.1 to; It is a range. Outside this range, it will be difficult to obtain effective effects.
  • the agent of the present invention When the agent of the present invention is used as a liver cancer occurrence / progression inhibitor for cirrhosis patients, its administration form / dosage form may be either oral administration or parenteral administration.
  • oral administration agents powders, granules, capsules Drugs, tablets, solids such as chewables, liquids such as solutions and syrups, and parenterals include injections and sprays. .
  • the agents and compositions of the present invention can be administered to animals (preferably, mammals such as humans).
  • the dose varies depending on the age, weight, pathology, and administration method of the subject patient, but the daily dose is usually 0.5 to 30 g isoleucine, 1.0 to 60 g leucine, 0.5 to 30 Use g as a guide.
  • the active ingredient of the pharmaceutical agent used for the purpose of treatment or prevention of the disease targeted by the present invention for the branched chain amino acids that are ingested or administered for other purposes, for example, from the need for a normal diet or for the treatment of other diseases, It is not necessary to include in the calculation.
  • Isoleucine, leucine and parin or their salts which are the active ingredients of the present invention, may be contained in the preparation each alone or in any combination, or all may be contained in one preparation. Also good. When separately formulated and administered, their administration route and dosage form may be the same or different, and the timing of administration of each may be simultaneous or different. It is determined as appropriate according to the type and effect of the drug used in combination.
  • the hepatocarcinogenesis / development inhibitor of the present invention may be a preparation containing a plurality of branched chain amino acids or their salts simultaneously, or a combined preparation in which each is separately formulated and used together. May be. All these forms are included. In particular, an embodiment in which all branched chain amino acids or their salts are contained in the same preparation is preferable because it can be easily administered.
  • the “weight ratio” indicates the ratio of the weight of each amino acid component in the preparation of the present invention and the la composition.
  • each active ingredient of isoloicin, mouth icin and valine is included in a single formulation, it is the ratio of the individual contents.
  • each minute is contained alone or in any combination in a plurality of preparations, it is the ratio of the weight of each active ingredient contained in each preparation.
  • each active ingredient is present in the form of a salt, it is the ratio when each is converted to the weight of the free form.
  • the actual dose ratio is the ratio of a single dose or daily dose of each active ingredient per administration subject (ie, patient).
  • the weight ratio corresponds to the dose ratio.
  • the ratio of the total amount of each active ingredient in each preparation administered once or daily corresponds to the weight ratio.
  • 0) is 10 g ZK g or more in the oral administration of mice.
  • the drug of the present invention is formulated into a solid agent such as powder, granule, capsule, tablet, chewable agent, solution such as solution, syrup, or injection, spray, etc. by a usual method. can do.
  • the drug of the present invention can be prepared by using an appropriate pharmaceutically acceptable carrier, for example, an excipient, a binder, a lubricant, a solvent, a disintegrating agent, a solubilizing agent, as required in the preparation. It is formulated with suspending agents, emulsifiers, tonicity agents, stabilizers, soothing agents, P preservatives, antioxidants, flavoring agents, coloring agents and the like. Furthermore, the composition of the present invention can be prepared together with the above carrier.
  • an appropriate pharmaceutically acceptable carrier for example, an excipient, a binder, a lubricant, a solvent, a disintegrating agent, a solubilizing agent, as required in the preparation. It is formulated with suspending agents, emulsifiers, tonicity agents, stabilizers, soothing agents, P preservatives, antioxidants, flavoring agents, coloring agents and the like.
  • the composition of the present invention can be prepared together with the above carrier.
  • Excipients include lactose, pudou sugar, sugars such as D-manntol, starches, organic excipients such as cellulose such as crystalline cellulose, and inorganic additives such as calcium carbonate and kaolin.
  • binders include arsenic starch, gelatin, arabic gum, methylsenololose, canoleboxymethinoresenorelose, canoleboximethylenosenorelose sodium, crystalline senorelose, D-mannitonole, toreno, loin, HI Droxypropinoresenorelose, Hydroxypropinoresmethinoresose, Polybi Ninorepyrrolidone, polybulal alcohol, etc.
  • lubricants include stearic acid, fatty acid salts such as stearate, tanolec, silicates, etc.
  • solvents include purified water, physiological saline, etc.
  • Examples include low-substituted hydroxypropyl cellulose, chemically modified cellulose and starches, and solubilizing agents include polyethylene glycolol, propylene glycolanol, trehalose, benzinole benzoate, ethanol, sodium carbonate Sodium citrate, sodium salicylate, sodium acetate, etc., as suspending agents or emulsifiers, sodium lauryl sulfate, gum arabic, gelatin, lecithin, glyceryl monostearate, polyvinyl alcohol, polyvinylpyrrolidone, carboxy Celluloses such as chilled cellulose sodium, polysorbates, polyoxyethylene hydrogenated castor oil, etc., as isotonizing agents, sodium chloride, potassium chloride, sugars, glycerin, urea, etc.
  • solubilizing agents include polyethylene glycolol, propylene glycolanol, trehalose, benzinole benzoate, ethanol, sodium carbonate Sodium citrate,
  • antioxidants Polyethylene glycol, sodium dextran sulfate, and other amino acids, as the soothing agent, glucose, calcium gnoleconate, pro-hydrochloride, etc., as preservatives, esters of paraoxybenzoate, chlorobutanol, Benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid, etc.
  • Antioxidants include sulfite and ascorbic acid, and flavoring agents are commonly used in the pharmaceutical and food fields. , Fragrances, etc. And coloring agents commonly used in the food field.
  • liver diseases such as interferon, glycyrrhizin, ursodeoxycholic acid, ribavirin, herbal medicine Sho-saiko-to and the like can be added to the drug and composition of the present invention.
  • Example 1 The incidence of liver cancer in patients with hepatitis C virus-positive cirrhosis with or without diabetes was investigated.
  • the weight ratio of isoleucine, leucine, and phosphorus was 1: 2: 1.2 (isoleucine: 0.952 g, leucine: 1.904 g, and phosphorus: 1.144 g)
  • Branched-chain amino acid preparation Libertate (registered trademark) granule (Ajinomoto Co., Inc.) 1 capsule at a time, 3 times a day after oral administration.
  • BMI body weight (Kg) / ⁇ height (m) ⁇ 2 .
  • the Tato administration group is based on diet, and the weight ratio of isoleucine, leucine, and parin is
  • results of examination of the incidence of liver cancer in 5 patients in liver cirrhosis patients with BMI ⁇ 25 and in 5 patients in the diet therapy group (group D) and 60 patients in the rebact group (group L) 2)
  • group D liver cirrhosis patients
  • group L 60 patients in the rebact group
  • 15 patients in the diet-treated group developed liver cancer
  • the dotted line represents the rebact group
  • the straight line represents the diet treatment group (non-leapact group).
  • the present invention provides a liver cancer growth / proliferation inhibitor comprising three branched chain amino acids of isoleucine, leucine, and valine, or a salt thereof, and a cirrhosis patient with diabetes and / or a BMI value. Suppresses the development and progression of liver cancer in patients with severe cirrhosis.
  • the present invention is particularly effective when the cirrhosis is decompensated cirrhosis.
  • the drug of the present invention since the drug of the present invention has an amino acid as an active ingredient, it is highly safe and has few side effects, so it can be administered over a long period of time. It can be used advantageously for therapy.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L’invention concerne un inhibiteur de l’apparition et/ou de la progression du cancer hépatique chez un patient avec une cirrhose active souffrant aussi de diabète et/ou ayant un BMI de 25 ou plus, contenant comme principes actifs trois types d'acides aminés ramifiés, à savoir l’isoleucine, la leucine et la valine, ou leurs sels.
PCT/JP2006/315893 2005-08-05 2006-08-04 Inhibiteur de l’apparition et de la progression du cancer hépatique Ceased WO2007018278A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2007529631A JP5067160B2 (ja) 2005-08-05 2006-08-04 肝癌発生・進展抑制剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005227454 2005-08-05
JP2005-227454 2005-08-05

Publications (1)

Publication Number Publication Date
WO2007018278A1 true WO2007018278A1 (fr) 2007-02-15

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WO (1) WO2007018278A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012111790A1 (fr) 2011-02-17 2012-08-23 味の素株式会社 Potentialisateur de l'activité antitumorale d'un agent chimiothérapique

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007018278A1 (fr) * 2005-08-05 2007-02-15 Ajinomoto Co., Inc. Inhibiteur de l’apparition et de la progression du cancer hépatique
JOP20190146A1 (ar) 2016-12-19 2019-06-18 Axcella Health Inc تركيبات حمض أميني وطرق لمعالجة أمراض الكبد
JP7266581B2 (ja) 2017-08-14 2023-04-28 アクセラ・ヘルス・インコーポレイテッド 肝疾患の治療のためのアミノ酸組成物
WO2019246225A1 (fr) 2018-06-20 2019-12-26 Axcella Health Inc. Compositions et procédés pour le traitement de l'infiltration de graisse dans le muscle

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06256186A (ja) * 1993-03-05 1994-09-13 Morishita Roussel Kk 癌用アミノ酸製剤
JP2003238401A (ja) * 2002-02-20 2003-08-27 Ajinomoto Co Inc 疾患の治療、改善又は予防用医薬品及び飲食品
WO2004058243A1 (fr) * 2002-12-26 2004-07-15 Ajinomoto Co., Inc. Inhibiteur de l'apparition et de l'evolution du cancer du foie
WO2005055997A1 (fr) * 2003-12-15 2005-06-23 Ajinomoto Co., Inc. Composition medicinale pour traiter et pour prevenir une maladie inflammatoire
JP2006028039A (ja) * 2004-07-13 2006-02-02 Masami Moriyama 肝線維症の予防方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007018278A1 (fr) * 2005-08-05 2007-02-15 Ajinomoto Co., Inc. Inhibiteur de l’apparition et de la progression du cancer hépatique

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06256186A (ja) * 1993-03-05 1994-09-13 Morishita Roussel Kk 癌用アミノ酸製剤
JP2003238401A (ja) * 2002-02-20 2003-08-27 Ajinomoto Co Inc 疾患の治療、改善又は予防用医薬品及び飲食品
WO2004058243A1 (fr) * 2002-12-26 2004-07-15 Ajinomoto Co., Inc. Inhibiteur de l'apparition et de l'evolution du cancer du foie
WO2005055997A1 (fr) * 2003-12-15 2005-06-23 Ajinomoto Co., Inc. Composition medicinale pour traiter et pour prevenir une maladie inflammatoire
JP2006028039A (ja) * 2004-07-13 2006-02-02 Masami Moriyama 肝線維症の予防方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012111790A1 (fr) 2011-02-17 2012-08-23 味の素株式会社 Potentialisateur de l'activité antitumorale d'un agent chimiothérapique

Also Published As

Publication number Publication date
JP2012214485A (ja) 2012-11-08
JPWO2007018278A1 (ja) 2009-02-19
JP5516654B2 (ja) 2014-06-11
JP5067160B2 (ja) 2012-11-07

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